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Synthesis and Glycosidase Inhibitory Activities of 5‐(1′,4′‐Dideoxy‐1′,4′‐imino‐ D ‐erythrosyl)‐2‐methyl‐3‐furoic Acid (=5‐[(3 S ,4 R )‐3,4‐Dihydroxypyrrolidin‐2‐yl]‐2‐methylfuran‐3‐carboxylic Acid) Derivatives: New Leads as Selective α ‐ L ‐Fucosidase and β ‐Galactosidase Inhibitors
Author(s) -
MorenoVargas Antonio J.,
Robina Inmaculada,
Demange Raynald,
Vogel Pierre
Publication year - 2003
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200390152
Subject(s) - chemistry , isopropyl , amide , stereochemistry , ethyl ester , ethyl acetoacetate , derivative (finance) , carboxylic acid , medicinal chemistry , organic chemistry , catalysis , financial economics , economics
The García‐González reaction of D ‐glucose and ethyl acetoacetate generated ethyl 5‐[(1′ S )‐ D ‐erythrosyl]‐2‐methyl‐3‐furoate ( 5 ), which was converted to ethyl 5‐[(1′ R )‐1′,4′‐dideoxy‐1′,4′‐imino‐ D ‐erythrosyl]‐2‐methyl‐3‐furoate ( 3c ) and to ethyl 5‐[(1′ S )‐1′,4′‐dideoxy‐1′,4′‐imino‐ D ‐erythrosyl]‐2‐methyl‐3‐furoate ( 4c ). Similar methods were developed to generate other carboxylic acid derivatives such as methyl (see 3e and 4e ), isopropyl (see 3f ), and butyl esters (see 3g ), S ‐phenyl (see 3a ) and S ‐ethyl thioesters (see 3m ), N ‐benzylcarboxamides 3b and 4b , glycine‐derived amide 3h , and N ‐phenyl (see 3i ), N ‐isopropyl (see 3j and 4j ), N , N ‐diethyl‐ (see 3k and 4k ), and N ‐ethyl‐carboxamides (see 3l ). All the new 5‐(1′,4′‐dideoxy‐1′,4′‐imino‐ D ‐erythrosyl)‐3‐furoic acid (=5‐[(3 S ,4 R )‐3,4‐dihydroxypyrrolidin‐2‐yl)furan‐3‐carboxylic acid) derivatives 3 and 4 were assayed for inhibitory activity towards 25 commercially available glycosidases. Derivative 3a with a S ‐phenyl thioester group is a good and selective α ‐ L ‐fucosidase inhibitor ( K i =2–4 μ M ), whereas 4b (with a N ‐benzylcarboxamide group) is a good β ‐galactosidase inhibitor.